Palladium-catalyzed enantioselective oxidations of alcohols using molecular oxygen
Palladium-catalyzed enantioselective oxidations of alcohols using molecular oxygen
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DOI：
10.1021/ja015827n
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发表时间：
2001-08-01
影响因子：
15
通讯作者：
Sigman, MS
中科院分区：
文献类型：
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作者：
Jensen, DR;Pugsley, JS;Sigman, MS
将分子氧作为化学计量的再氧化剂与催化金属结合使用对于有机合成中的应用具有特殊的实际优势。 1 这部分是由于与分子氧相关的有利经济效益以及氧化歧管中环境友好的副产品（水和过氧化氢）的形成。在有机合成中使用分子氧的一个很好的例子是醇到醛和酮的金属催化有氧氧化。 2, 3 我们对将这些氧化的范围扩展到不对称催化产生了兴趣。 4 为此，我们设想了两个潜在有用的反应：(1) 外消旋仲醇的氧化动力学拆分，5 个先前使用酰化 6 和氧化完成的动力学拆分，7, 8 和 (2) 内消旋二醇的氧化去对称化。 9 在此，我们报告了一种由 Pd (II) 和手性二胺介导的便捷的对映选择性醇有氧氧化反应。已有报道使用催化 Pd (II) 盐对醇进行有氧氧化。 3a-d 特别令人感兴趣的是胺添加剂3a-c 既能影响配体加速催化10 又能扩展底物范围。因此，除了 Pd 介导的不对称反应的常见配体之外，我们还通过筛选各种手性胺配体开始了对氧化动力学拆分催化剂的研究（表 1，等式 1）。双齿和三齿配体通常是较差的氧化模板，转化率较低（条目 b、f、g 和 h）。相比之下，由 3 位取代的吡啶配体衍生的 Pd (II) 配合物尽管 krel 值较低，但转化率较高（条目 c 和 e）。初步筛选最有希望的结果是 (-)-金雀花碱（一种手性叔二胺）给出了最好的 krel (2.6)。为了提高反应速率和krel，对(-)-金雀花/Pd (II)催化剂体系的反应参数进行了优化。在相同的温度和氧气压力（气球压力）下同时检查单个装置中的十个反应参数。 12, 13 在每次筛选期间，使用配备手性柱的自动进样 GC 定期分析等分试样。优化程序使我们能够有效地检查溶剂、组分浓度、Pd (II) 源和分子筛14 对 krel 和反应速率的影响。筛选这些参数后，确定了两组条件。条件A：1, 2-二氯乙烷、15 20 mol%(-)-金雀花石和5 mol% Pd(OAc) 2 中的0.5 M 1a 和条件B：1, 2-二氯乙烷、20 mol%(-)-金雀花石和5 mol% 可溶性PdCl 2 源(Pd (MeCN))中的0.25 M 1a 2Cl2 和 Pd-(COD) Cl2 给出了类似的结果）。使用这两种条件评估温度的影响。对于Pd(OAc) 2 ，发现温度对对映选择性具有显着影响，其中60℃的温度给出最高的krel值，而对于PdCl 2 源没有观察到显着的温度影响。总体而言，对于 1a，使用条件 B 将初始条件从 2.6 的 krel 优化到 17.5。接下来，评估了氧化动力学拆分的底物范围（表 2）。在这两种条件下，苄基仲醇通常是氧化动力学拆分的良好底物，krel 值范围为 8.7 至 23.6。使用钯-
The use of molecular oxygen as a stoichiometric reoxidant in combination with a catalytic metal has exceptional practical advantages for applications in organic synthesis. 1 This is in part due to the favorable economics associated with molecular oxygen and the formation of environmentally benign byproducts in the oxidation manifold (water and hydrogen peroxide). An excellent example of the use of molecular oxygen in organic synthesis is the metal-catalyzed aerobic oxidation of alcohols to aldehydes and ketones. 2, 3 We became interested in extending the scope of these oxidations to asymmetric catalysis. 4 To this end, we envisioned two potentially useful reactions:(1) the oxidative kinetic resolution of racemic secondary alcohols, 5 kinetic resolutions that have previously been accomplished using acylation6 and oxidation, 7, 8 and (2) the oxidative desymmetrization of meso-diols. 9 Herein we report a convenient, enantioselective aerobic oxidation of alcohols mediated by Pd (II) and a chiral diamine. Aerobic oxidations of alcohols using catalytic Pd (II) salts have been reported. 3a-d Of particular interest is the observation that amine additives3a-c both effect ligand-accelerated catalysis10 and extend the substrate scope. Therefore, we initiated our investigation for an oxidative kinetic resolution catalyst by screening various chiral amine ligands in addition to common ligands for Pd-mediated asymmetric reactions (Table 1, eq 1). Bi-and tridentate ligands were generally poor templates for oxidation giving low conversions (entries b, f, g, and h). In contrast, Pd (II) complexes derived from pyridine ligands with 3-substitution gave high conversions, albeit with low krel values11 (entries c and e). The most promising result from this initial screen was that (-)-sparteine, a chiral tertiary diamine, gave the best krel (2.6). To improve both the reaction rate and krel, the reaction parameters of the (-)-sparteine/Pd (II) catalyst system were optimized. Ten reaction parameters in a single apparatus were simultaneously examined under identical temperature and oxygen pressure (balloon pressure). 12, 13 During each screen, aliquots were periodically analyzed using an autosampling GC equipped with a chiral column. The optimization procedure allowed us to efficiently examine the effect of solvent, component concentration, Pd (II) source, and molecular sieves14 on krel and reaction rate. After screening these parameters, two sets of conditions were identified. Conditions A: 0.5 M 1a in 1, 2-dichloroethane, 15 20 mol%(-)-sparteine, and 5 mol% of Pd (OAc) 2 and conditions B: 0.25 M 1a in 1, 2-dichloroethane, 20 mol%(-)-sparteine, and 5 mol% of a soluble PdCl2 source (Pd (MeCN) 2Cl2 and Pd-(COD) Cl2 gave similar results). Using both conditions the effect of temperature was evaluated. For Pd (OAc) 2, the temperature was found to have a significant influence on enantioselectivity wherein a temperature of 60 C gave the highest krel value, while no significant temperature effect was observed for PdCl2 sources. Overall for 1a, the initial conditions were optimized from a krel of 2.6 to 17.5 using conditions B. Next, the substrate scope of the oxidative kinetic resolution was evaluated (Table 2). Using both conditions, benzylic secondary alcohols are generally good substrates for oxidative kinetic resolution with krel values ranging from 8.7 to 23.6. Using Pd-